The electrospray process consists of flowing sample liquid through a small tube or capillary which is maintained at a high voltage with respect to a nearby surface. The liquid is dispersed into fine electrically charged droplets by the voltage gradient of the tip of the capillary. The ionization mechanism involves the desorption at atmospheric pressure of ions from the fine electrically charged particles. In many cases a heated gas is flowed in counter current to the electrospray to enhance dissolution of the electrospray droplets. The ions created by the electrospray are then mass analyzed in a mass analyzer such as a mass spectrometer.
Under the appropriate conditions, the electrospray resembles a symmetrical cone consisting of a very fine mist (or fog) of droplets (ca. 1 .mu.m in diameter). Excellent sensitivity and ion current stability can be obtained if the fine mist is produced. Unfortunately, the electrospray "quality" is highly dependent on the bulk properties of the solution being analyzed. The most important of which are surface tension and conductivity. A poor quality electrospray may contain larger droplets (&gt;10 .mu.m diameter) or a non-dispersed droplet stream. Larger droplets lead to decreased sensitivity. In addition, sputtering may occur. The partially desolvated droplets pass into a vacuum system causing sudden increases in pressure and instabilities in the ion current from a mass spectrometer.
Stable electrosprays are more difficult to obtain in the negative ion mode than in the positive ion mode due to the onset of corona discharge at lower voltages. Corona is facilitated in the negative mode due to the strong negative potential at the needle, which favors emission of electrons from the needle surface. Corona is detrimental to the electrospray process since the plasma produced creates a space-charged region that shields the tip of the needle from the electric fields necessary for droplet dispersion.
Low surface tension is preferable since electrostatic dispersion of droplets only occurs when coulomb forces exceed those due to surface tension. Most organic solvents have low surface tension (e.g., methanol, .gamma.=24 dynes/cm) and are readily electrosprayed; however, water has a very high surface tension (.gamma.=72 dynes/cm) and cannot be directly electrosprayed. Unfortunately, one may not simply increase the electrospray voltage to spray 100% water, since the onset of corona occurs before water can be effectively dispersed. Organic solvents can be mixed with water to lower surface tension for electrospray compatibility; however, for many chromatographic applications, the use of high percentages of organic solvents may impose serious compromises on the separations.
High solution conductivities also degrade electrospray performance. Although the reasons for this are not fully understood, it is believed that the charge density becomes too high for efficient separation of opposite charges at the tip of the needle. In any case, our experience is that ESI efficiency decreases dramatically as ionic strength is increased beyond 10.sup.-3 Molar.
One particularly important application of ESI is its use with reverse phase high-performance liquid chromatography (HPLC). In particular, for separations of peptides and proteins, gradients from 100% H.sub.2 O to 40% H.sub.2 O/60% acetonitrile are most often required. In addition, 0.1% trifluoroacetic acid (TFA) is usually added to both solvents to improve the separation quality. Since TFA is a relatively strong acid, its presence at the 0.1% level leads to high solution conductivity and poor electrospray quality. This combination of high water content and high solution conductivity makes it impossible to perform LC/MS with traditional electrospray.
There have been a number of attempts to provide an improved electrospray ion source. Mock et al., J.Chem Phys 52, 10 (1970) teach that the electrospray formation and evaporation rates can be improved by flowing nitrogen through the cylindrical span between the capillary needle and a surrounding tube past the tip of the needle. Henion teaches much the same technique in U.S. Pat. 4,861,988. Smith et al. U.S. Pat. 4,842,701 teaches the use of liquid sheath flow past the end of the needle. The liquid sheath is used to reduce the sample liquid surface tension. It has been suggested that these two techniques can be combined to provide a pneumatically assisted liquid sheath.